Post-switch Effectiveness of Etanercept Biosimilar Versus Continued Etanercept in Rheumatoid Arthritis Patients with Stable Disease: A Prospective Multinational Observational Study.

INTRODUCTION: To better inform clinicians about the use of etanercept biosimilar (SB4) in patients with rheumatoid arthritis (RA), COMPANION-B, a prospective real-world observational study, evaluated the effectiveness of the voluntary switch from originator (etanercept, ETN) to SB4 in patients with stable RA (low-disease activity/remission). METHODS: The study recruited adult patients (18 years or older) with RA (2010 American College of Rheumatology criteria) prescribed ETN as their first or second biologic for at least 6 months across 14 sites in Canada and five in Australia. Patients had stable disease (Disease Activity Score-28 using erythrocyte sedimentation rate [DAS28-ESR] less than 3.2) at enrollment with no evidence of flare within the previous 3 months. Concomitant disease-modifying antirheumatic drugs (DMARDs) were permitted. Patients could elect to continue ETN or voluntarily switch to SB4 in consultation with their doctors. The primary effectiveness measure was the proportion of patients with disease worsening (defined as a DAS28-ESR increase of at least 1.2 from baseline and minimum score of at least 3.2 or a defined modification in RA treatment) during 12 months of follow-up. The secondary effectiveness measure was the proportion of patients with disease worsening at month 6. Serious adverse events (SAEs) and non-serious adverse reactions (NSARs) were recorded. RESULTS: Of 163 patients enrolled, 109 elected to continue on ETN and 54 switched to SB4; 65.8% of patients received non-biologic DMARD(s), 52.6% methotrexate, and 10.5% oral corticosteroid(s). At month 12, the proportion of patients with disease worsening was comparable in the ETN group (22.8% [95% CI 15.0-32.2]) and SB4 group (17.6% [95% CI 8.4-30.9]). Similarly, the proportions of patients with disease worsening were also comparable at month 6 (ETN: 7.9% [95% CI 3.5-15.0]; SB4: 7.8% [95% CI 2.2-18.9]). SAEs were low and similar across both groups (ETN: 8.7%; SB4: 5.7%). NSARs were slightly higher in the SB4 vs. ETN group (13.2% vs. 2.9%). CONCLUSIONS: SB4 demonstrated comparable effectiveness to ETN over 12 months in patients with stable RA who voluntarily switched to the biosimilar in a real-world setting.

Genetic modulation of longitudinal change in neurocognitive function among adult glioma patients.

PURPOSE: Impaired neurocognitive function (NCF) is extremely common in patients with higher grade primary brain tumor. We previously reported evidence of genetic variants associated with NCF in glioma patients prior to treatment. However, little is known about the effect of genetic variants on NCF decline after adjuvant therapy. METHODS: Patients (N = 102) completed longitudinal NCF assessments that included measures of verbal memory, processing speed, and executive function. Testing was conducted in the postoperative period with an average follow up interval of 1.3 years. We examined polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase). RESULTS: Five polymorphisms were associated with longitudinal changes in processing speed and 14 polymorphisms with executive function. Change in processing speed was strongly associated with MCPH1 rs17631450 (P = 2.2 × 10-7) and CCDC26 rs7005206 (P = 9.3 × 10-7) in the telomerase pathway; while change in executive function was more strongly associated with FANCF rs1514084 (P = 2.9 × 10-6) in the DNA repair pathway and DAOA rs12428572 (P = 2.4 × 10-5) in the cognitive pathway. Joint effect analysis found significant genetic-dosage effects for longitudinal changes in processing speed (Ptrend = 1.5 × 10-10) and executive function (Ptrend = 2.1 × 10-11). In multivariable analyses, predictors of NCF decline included progressive disease, lower baseline NCF performance, and more at-risk genetic variants, after adjusting for age, sex, education, tumor location, histology, and disease progression. CONCLUSION: Our longitudinal analyses revealed that polymorphisms in telomerase, DNA repair, and cognitive pathways are independent predictors of decline in NCF in glioma patients.

Comparative effectiveness of first-line tumour necrosis factor inhibitor versus non-tumour necrosis factor inhibitor biologics and targeted synthetic agents in patients with rheumatoid arthritis: results from a large US registry study.

OBJECTIVES: This study evaluated the comparative effectiveness of a tumour necrosis factor inhibitor (TNFi) versus a non-TNFi (biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs)) as the first-line treatment following conventional synthetic DMARDs, as well as potential modifiers of response, observed in US clinical practice. METHODS: Data were from a large US healthcare registry (Consortium of Rheumatology Researchers of North America Rheumatoid Arthritis Registry). The analysis included patients (aged ≥18 years) with a documented diagnosis of rheumatoid arthritis (RA), a valid baseline Clinical Disease Activity Index (CDAI) score of >2.8 and no prior bDMARD or tsDMARD use. Outcomes were captured at 1-year postinitiation of a TNFi (adalimumab, etanercept, certolizumab pegol, golimumab or infliximab) or a non-TNFi (abatacept, tocilizumab, rituximab, anakinra or tofacitinib) and included CDAI, 28-Joint Modified Disease Activity Score, patient-reported outcomes (including the Health Assessment Questionnaire Disability Index, EuroQol-5 Dimension score, sleep, anxiety, morning stiffness and fatigue) and rates of anaemia. Groups were propensity score-matched at baseline to account for potential confounding. RESULTS: There were no statistically significant differences observed between the TNFi and non-TNFi treatment groups for outcomes assessed, except the incidence rate ratio for anaemia, which slightly favoured the TNFi group (19.04 per 100 person-years) versus the non-TNFi group (24.01 per 100 person-years, p=0.03). No potential effect modifiers were found to be statistically significant. CONCLUSIONS: The findings of no significant differences in outcomes between first-line TNF versus first-line non-TNF groups support RA guidelines, which recommend individualised care based on clinical judgement and consideration of patient preferences.

Evaluation of Changes in Skin and Joint Outcomes and Associated Treatment Changes in Psoriatic Arthritis (PsA): Experience From the Corrona PsA/SpA Registry.

OBJECTIVE: To characterize skin severity and joint activity outcomes and associated treatment changes in patients with psoriatic arthritis (PsA) through 12 months of follow-up after enrollment in the Corrona Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry. METHODS: Patients ≥ 18 years of age with a diagnosis of PsA and a history of psoriasis between March 21, 2013, and September 30, 2016, were enrolled (n = 647). Demographics, clinical features, and treatment characteristics were collected and stratified by skin severity and joint activity. Change in joint and skin from enrollment to the 12-month visit was classified by change in category of Clinical Disease Activity Index (CDAI) or body surface area (BSA). Tests of association evaluated the relationship between changes in therapy and changes in skin severity and joint activity. RESULTS: Patients with improvement in both joint activity and skin severity saw the largest median reduction in both CDAI and BSA, while those who worsened in both had the greatest median increase in both CDAI and BSA. The majority of PsA patients (> 50%) had no change in skin severity regardless if they had reduced therapy (50%), no therapy changes (54%), or increased therapy (56%; P = 0.5875). However, there was a significant association between changes in therapy and changes in joint activity (P < 0.001). Patients who increased therapy were more likely to have improvement in joint activity (32%) compared to patients who reduced therapy (22%) or had no therapy changes (11%). CONCLUSION: The clinical implication for our findings suggests the assessment and incorporation of both skin and joint components may be advisable.

Effectiveness of Tocilizumab in Patients with Rheumatoid Arthritis Is Unaffected by Comorbidity Burden or Obesity: Data from a US Registry.

OBJECTIVE: Comorbidity burden and obesity may affect treatment response in patients with rheumatoid arthritis (RA). Few real-world studies have evaluated the effect of comorbidity burden or obesity on the effectiveness of tocilizumab (TCZ). This study evaluated TCZ effectiveness in treating RA patients with high versus low comorbidity burden and obesity versus nonobesity in US clinical practice. METHODS: Patients in the Corrona RA registry who initiated TCZ were stratified by low or high comorbidity burden using a modified Charlson Comorbidity Index (mCCI) and by obese or nonobese status using body mass index (BMI). Improvements in disease activity and functionality after TCZ initiation were compared for the above strata of patients at 6 and 12 months after adjusting for statistically significant differences in baseline characteristics. RESULTS: We identified patients with high (mCCI ≥ 2; n = 195) and low (mCCI < 2; n = 575) comorbidity burden and patients categorized as obese (BMI ≥ 30; n = 356) and nonobese (BMI < 30; n = 449) who were treated with TCZ. Most patients (> 95%) were biologic experienced and about one-third of patients received TCZ as monotherapy, with no significant differences between patients by comorbidity burden or obesity status. Improvement in disease activity and functionality at 6 and 12 months was similar between groups, regardless of comorbidity burden or obesity status. CONCLUSION: In this real-world analysis, TCZ was frequently used to treat patients with high comorbidity burden or obesity. Effectiveness of TCZ did not differ by comorbidity or obesity status.

Molecular profiling of rheumatoid arthritis patients reveals an association between innate and adaptive cell populations and response to anti-tumor necrosis factor.

BACKGROUND: The goal of this study is to use comprehensive molecular profiling to characterize clinical response to anti-TNF therapy in a real-world setting and identify reproducible markers differentiating good responders and non-responders in rheumatoid arthritis (RA). METHODS: Whole-blood mRNA, plasma proteins, and glycopeptides were measured in two cohorts of biologic-naïve RA patients (n = 40 and n = 36) from the Corrona CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory coNditions) registry at baseline and after 3 months of anti-TNF treatment. Response to treatment was categorized by EULAR criteria. A cell type-specific data analysis was conducted to evaluate the involvement of the most common immune cell sub-populations. Findings concordant between the two cohorts were further assessed for reproducibility using selected NCBI-GEO datasets and clinical laboratory measurements available in the CERTAIN database. RESULTS: A treatment-related signature suggesting a reduction in neutrophils, independent of the status of response, was indicated by a high level of correlation (ρ = 0.62; p < 0.01) between the two cohorts. A baseline, response signature of increased innate cell types in responders compared to increased adaptive cell types in non-responders was identified in both cohorts. This result was further assessed by applying the cell type-specific analysis to five other publicly available RA datasets. Evaluation of the neutrophil-to-lymphocyte ratio at baseline in the remaining patients (n = 1962) from the CERTAIN database confirmed the observation (odds ratio of good/moderate response = 1.20 [95% CI = 1.03-1.41, p = 0.02]). CONCLUSION: Differences in innate/adaptive immune cell type composition at baseline may be a major contributor to response to anti-TNF treatment within the first 3 months of therapy.

Persistence of tumor necrosis factor inhibitor or conventional synthetic disease-modifying antirheumatic drug monotherapy or combination therapy in psoriatic arthritis in a real-world setting.

This study described treatment patterns in a psoriatic arthritis (PsA) patient registry for new or ongoing tumor necrosis factor inhibitor (TNFi) monotherapy, conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, or TNFi/csDMARD combination therapy. This retrospective analysis included adults with PsA who enrolled in the Corrona PsA/spondyloarthritis registry between March 21, 2013 (registry initiation), and January 31, 2017, and received an approved TNFi and/or csDMARD as "existing use" starting before registry entry or "initiated use" starting on/after registry entry. Therapy persistence was defined as index therapy use for ≥ 12 months without a treatment gap of ≥ 30 days. Among the evaluable patients with existing TNFi monotherapy (n = 251), csDMARD monotherapy (n = 225), and combination therapy (n = 214), 93, 87, and 87% were persistent for ≥ 12 months, and another 6, 5, and 5%, respectively, had no change with < 12 months of follow-up after first use. Among evaluable patients who initiated use of TNFi monotherapy (n = 26), csDMARD monotherapy (n = 35), and combination therapy (n = 15), 50, 43, and 53% were persistent for ≥ 12 months, and another 27, 20, and 20%, respectively, had no change with < 12 months of follow-up after first use. After initiation of index therapy, most changes (19-27% of patients) were discontinuation; 4-13% switched biologic therapy during follow-up. The results of this analysis of real-world treatment patterns in a PsA patient registry suggest that nonpersistence for TNFi monotherapy, csDMARD monotherapy, or TNFi/csDMARD combination therapy occurs more commonly after initiation of therapy than in patients with existing therapy. Trial registration: NCT02530268.

Patterns of Prednisone Use in Patients with Rheumatoid Arthritis Initiating Treatment with Tocilizumab in Routine US Clinical Practice.

INTRODUCTION: Prednisone is frequently administered in combination with other therapies for the treatment of rheumatoid arthritis (RA); however, its chronic use is associated with an increased risk of comorbidities and mortality. The objective of this analysis was to evaluate changes in prednisone use among patients with RA treated with tocilizumab (TCZ) in routine US clinical practice. METHODS: TCZ-naïve patients in the Corrona RA registry who initiated TCZ were included. The primary outcome was the proportion of patients with changes in prednisone use over 12 months (primary analysis) and 6 months (secondary analysis). Changes in disease activity over 6 and 12 months (± 3 months) were assessed using the Clinical Disease Activity Index (CDAI). Outcomes were assessed in the overall population and separately for patients receiving TCZ monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs. RESULTS: Of patients receiving prednisone at baseline (mean [SD] dose: 7.7 [5.2] mg/day), 30.6% discontinued prednisone over 12 months; among patients receiving > 7.5 mg of prednisone at the time of TCZ initiation, 63.0% discontinued prednisone or decreased their dose by ≥ 5 mg over 12 months. In secondary analyses, 29.7% of patients receiving prednisone at baseline had discontinued prednisone over 6 months; among those receiving > 7.5 mg of prednisone at baseline, 51.3% discontinued or decreased their dose by ≥ 5 mg over 6 months. Changes in prednisone use and improvement from baseline in CDAI score over 6 and 12 months were comparable between patients who initiated TCZ monotherapy vs. TCZ combination therapy. CONCLUSIONS: In this real-world analysis, many patients initiating TCZ monotherapy or combination therapy were able to discontinue or decrease their prednisone dose over 12 months. Similar changes in prednisone dose were observed over 6 months. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01402661. FUNDING: Corrona, LLC and Genentech, Inc. Plain language summary available for this article.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint damage and disability. The steroid prednisone is a fast-acting and effective treatment for RA and is often prescribed alongside disease-modifying antirheumatic drugs (DMARDs). The health risks associated with the long-term use of prednisone have led to recommendations to minimize prednisone dose and duration of treatment. Few studies have examined the extent to which biologic DMARDs allow rheumatologists to reduce or discontinue the use of prednisone. The objective of this study was to evaluate changes in prednisone dose while receiving tocilizumab (TCZ) in patients with RA seen in routine US clinical practice. Patients who were enrolled in the Corrona RA registry and were beginning treatment with TCZ were included. Changes in prednisone use were evaluated 12 months after starting treatment. Of patients receiving prednisone at study initiation, 30.6% had discontinued prednisone over 12 months; among patients receiving > 7.5 mg of prednisone at the time of TCZ initiation, 63.0% discontinued prednisone or decreased the dose by ≥ 5 mg over 12 months. In secondary analyses, 29.7% of patients receiving prednisone at study initiation had discontinued prednisone over 6 months; among those receiving > 7.5 mg of prednisone at baseline, 51.3% discontinued or decreased the dose by ≥ 5 mg over 6 months. Changes in prednisone use and improvement in disease activity over 6 and 12 months were comparable between patients who initiated TCZ monotherapy or combination therapy with other DMARDs.

Understanding the association between skin involvement and joint activity in patients with psoriatic arthritis: experience from the Corrona Registry.

Objective: To compare the characteristics of patients with psoriatic arthritis among patient groups stratified by degree of skin and joint involvement, and to evaluate the relationship between skin severity and joint activity. Methods: Body surface area (BSA) and Clinical Disease Activity Index (CDAI) at enrolment were analysed. Patient characteristics were stratified by skin severity and joint activity. Baseline patient characteristics, clinical and disease characteristics and patient-reported outcomes were compared. The strength of the relationship of skin severity and joint activity was evaluated using methods for categorical variables (χ2 test, Cramer's V) and continuous variables (linear regression). Results: 1542 adult patients in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry enrolled between 21 May 2013 and 20 September 2016 were analysed. Most patients in the BSA >3%/CDAI moderate/high subgroup had worse clinical and patient-reported outcomes. A significant (p<0.001) modest association (Cramer's V=0.1639) between skin severity and joint activity was observed among all patients at enrolment. Patients with higher skin severity were two times more likely to have higher joint involvement (OR 2.27, 95% CI 1.71 to 3.01). A significant linear relationship between CDAI and BSA was observed. Effect modification showed this linear relationship was modified by age, gender, insurance, work status, current therapy, Health Assessment Questionnaire, Nail visual analogue scale, minimal disease activity, dactylitis count, patient-reported pain and fatigue. Conclusion: Skin severity is modestly correlated with joint activity, and patients with higher skin severity are two times more likely to have increased joint involvement. Clinicians need to address both skin severity and joint activity in treatment decisions.

Adjustment of the multi-biomarker disease activity score to account for age, sex and adiposity in patients with rheumatoid arthritis.

OBJECTIVE: To develop and evaluate an adjusted score for the multi-biomarker disease activity (MBDA) test to account for the effects of age, sex and adiposity in patients with RA. METHODS: Two models were developed to adjust MBDA score for age, sex and adiposity, using either serum leptin concentration or BMI as proxies for adiposity. Two cohorts were studied. A cohort of 325 781 RA patients who had undergone commercial MBDA testing and had data for age, sex and serum leptin concentration was used for both models. A cohort of 1411 patients from five studies/registries with BMI data was used only for the BMI-adjusted MBDA score. Univariate and multivariate linear regression analyses evaluated the adjusted MBDA scores and conventional clinical measures as predictors of radiographic progression, assessed in terms of modified total Sharp score (ΔmTSS). RESULTS: Two models were developed, based on findings that MBDA score was higher in females than males and increased with age, leptin concentration and BMI. In pairwise regression analyses, the leptin-adjusted (P = 0.00066) and BMI-adjusted (P = 0.0027) MBDA scores were significant independent predictors of ΔmTSS after adjusting for DAS28-CRP, whereas DAS28-CRP was not, after adjusting for leptin-adjusted (P = 0.74) or BMI-adjusted (P = 0.87) MBDA score. Moreover, the leptin-adjusted MBDA score was a significant predictor of ΔmTSS after adjusting for the BMI-adjusted MBDA score (P = 0.025) or the original MBDA score (0.027), whereas the opposite was not true. CONCLUSION: Leptin-adjusted MBDA score significantly adds information to DAS28-CRP and the original MBDA score in predicting radiographic progression. It may offer improved clinical utility for personalized management of RA.

Association between melanoma and renal-cell carcinoma for sequential diagnoses: A single-center retrospective study.

BACKGROUND: Melanoma and renal-cell carcinoma (RCC) are known to be immunological neoplasms. Previous studies have shown increased risks in patients with melanoma of developing RCC and in those with RCC of developing melanoma. However, data regarding immunocompromised status in these patients are lacking. METHODS: We conducted a retrospective review of patients who had a diagnosis of melanoma and/or RCC. Using summary statistics, we calculated total person-years at risk for developing melanoma among patients with RCC and for developing RCC among patients with melanoma, and compared the results with the SEER data. We also assessed medical history related to immune status and the use of immunosuppressive drugs. RESULTS: Among 13,879 patients with melanoma and 7597 patients with RCC, 89 had diagnoses of both melanoma and RCC (0.6% and 1.2% of melanoma and RCC patients, respectively): eight were diagnosed with both cancers concurrently, 54 were diagnosed with melanoma first, and 27 were diagnosed with RCC first. Standardized incidence ratios (SIRs) were 2.87 (95%CI 2.16-3.74) for developing RCC among the melanoma patients and 2.31 (95%CI 1.52-3.37) for developing melanoma among the RCC patients, compared to age-, sex-, race-, and calendar-specific adjusted incidence rates of each cancer in the SEER registry. None of the 81 patients with sequential diagnoses had a history of immunocompromised disease, nor did they receive chronic immunosuppressive drugs. Only two received chemotherapy and/or radiotherapy. CONCLUSION: We demonstrated a strong association between the diagnoses of melanoma and RCC. These increased risks could not be attributed to either immune status or previous antineoplastic treatment.

The cytokinesis-blocked micronucleus assay as a novel biomarker for selection of lung cancer screening participants.

BACKGROUND: Despite the promising results of the National Lung Screening Trial in reducing lung cancer mortality among high risk smokers, several challenges remain to be addressed. These include the high false positive rates and the large number of smokers screened in order to prevent one lung cancer death. In addition, host genetic susceptibility has not been integrated into selection of who should be screened. These challenges highlight the need to develop robust ways to identify susceptible smokers for appropriate screening. METHODS: We used the cytokinesis block micronucleus (CBMN) assay to assess smoking induced genetic instability among NLST participants. Blood cultures were prepared at time of entry into the screening study and DNA damage was recorded as the frequency of binucleated nucleoplasmic bridges and micronuclei. Low dose CT (LDCT) and chest X-ray (CXR) image findings were available upon unblinding of the NLST study and imaging data were merged with blood marker data for statistical analysis. RESULTS: A total of 641 participants were included in this study. The frequency of the CBMN endpoints at time of entry into the study was significantly higher among study participants who had a positive finding during the 3-year screening or reported lung cancer at the end of the follow-up period as compared to participants who were negative. Growth curve models were used to compare trajectories of change in CBMN endpoints between entry into the study and end-of-screening period. A statistically significant increase was predicted for CBMN endpoints among the study participants who were positive versus those who remained negative at the end-of-screening period (P<0.001). CONCLUSIONS: Genetic instability biomarkers have the potential of facilitating the identification of genetically susceptible high-risk smokers who would benefit from targeted lung screening programs.

Disease activity and biologic use in patients with psoriatic arthritis or rheumatoid arthritis.

To compare disease burden and biologic use among psoriatic arthritis (PsA) or rheumatoid arthritis (RA) patients recruited to the Corrona registry. Retrospective study of patients with PsA or RA enrolled in Corrona between January 2002 and March 2013 and grouped in 2-year intervals. Clinical outcomes and biologic use were assessed. Biologic use increased over time in both cohorts, with 62 and 52% of patients with PsA and RA, respectively, receiving biologics by 2012-2013. However, 25 and 35% of patients with PsA and RA, respectively, continued to experience moderate/high disease activity. Overall, the progressive increase in biologic use accompanied progressive decreases in Clinical Disease Activity Index (from 14.2 to 10.4 for RA, and 12.4 to 8.1 for PsA) and mean Health Assessment Questionnaire score (from 0.36 to 0.34, and 0.3 to 0.24). Mean patient pain, the proportion of patients reporting morning stiffness, and the mean duration of morning stiffness remained similar for both cohorts. PsA and RA treated in the rheumatology setting had a comparable impact on patient quality of life and functional ability. Disease burden improved with increased biologic utilization in both groups; however, moderate/severe disease remains in a significant proportion of PsA and RA patients.

Chronic obstructive pulmonary disease among lung cancer-free smokers: The importance of healthy controls.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) in smokers enrolled as "healthy" controls in studies is 10-50%. The COPD status of ideal smoker populations for lung cancer case-control studies should be checked via spirometry; however, this is often not feasible, because no medical indications exist for asymptomatic smokers to undergo spirometry prior to study enrollment. Therefore, there is an unmet need for robust, cost effective assays for identifying undiagnosed lung disease among asymptomatic smokers. Such assays would help excluding unhealthy smokers from lung cancer case-control studies. METHODS: We used the cytokinesis-blocked micronucleus (CBMN) assay (a measure of genetic instability) to identify undiagnosed lung disease among asymptomatic smokers. We used a convenience population from an on-going lung cancer case-control study including smokers with lung cancer (n = 454), smoker controls (n = 797), and a self-reported COPD (n = 200) contingent within the smoker controls. RESULTS: Significant differences for all CBMN endpoints were observed when comparing lung cancer to All controls (which included COPD) and Healthy controls (with no COPD). The risk ratio (RR) was increased in the COPD group vs. Healthy controls for nuclear buds (RR 1.28, 95% confidence interval 1.01-1.62), and marginally increased for micronuclei (RR 1.06, 0.98-1.89) and nucleoplasmic bridges (RR 1.07, 0.97-1.15). CONCLUSION: These findings highlight the importance of using truly healthy controls in studies geared toward assessment of lung cancer risk. Using genetic instability biomarkers would facilitate the identification of smokers susceptible to tobacco smoke carcinogens and therefore predisposed to either disease.

Performance of the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis in a geographically distant National Register-based cohort: an external validation.

BACKGROUND: Cardiovascular (CV) risk stratification for patients with rheumatoid arthritis (RA) should facilitate evidence-based management. Prior work has derived an internally validated a CV risk score, the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA), using US data. The aim of this study was to perform an external validation among unselected patients with RA from Europe. METHODS: Three large, partially overlapping, cohorts of patients with RA from the Swedish Rheumatology Quality register were identified for external validation, two with information on smoking and two with close to 10 years of median follow-up. The 10 -year rate of first CV events was assessed using the Kaplan-Meier method. The performance of ERS-RA was assessed using C-index and comparisons of observed versus predicted risks. RESULTS: The C-index for ERS-RA varied across the three RA cohorts, from 0.75 to 0.78. Predicted risks corresponded well to observed risks among individuals with ≤10 % observed 10- year CV risk, but underestimated risk in individuals with a higher observed risk. In the absence of data on smoking, ERS-RA underestimated the CV risk by 3.3%, whereas in the cohorts including data on smoking, the calibration was within 1% (0.06% and 0.7%). In the clinically relevant risk intervals (<5%, 5.0%-<7.5%, 7.5%-<10%), ERS-RA performed well. CONCLUSIONS: In an unselected Swedish population with RA, ERS-RA performed well, although the 10-year CV risk was underestimated in high-risk groups and in the absence of data on smoking. ERS-RA could be considered as a risk stratification tool for targeted preventive interventions in clinical rheumatology practice.

Rebound in Measures of Disease Activity and Symptoms in Corrona Registry Patients with Psoriatic Arthritis Who Discontinue Tumor Necrosis Factor Inhibitor Therapy after Achieving Low Disease Activity.

OBJECTIVE: Rebound may occur in patients with psoriatic arthritis (PsA) who discontinue TNF inhibitor (TNFi) therapy in low disease activity (LDA). METHODS: Using physician and patient reports, we quantified rebound following TNFi discontinuation [defined as Clinical Disease Activity Index (CDAI) score > 10 or TNFi restart] and time to rebound in adults with PsA in LDA (CDAI score ≤ 10) at TNFi discontinuation. RESULTS: Rebound occurred in 73% (69/94) of patients soon after discontinuation (median time to rebound 8.0 mos, 95% CI 6.0-12.0). CONCLUSION: Rebound occurred frequently in patients with PsA after TNFi discontinuation. TNFi discontinuation after achieving LDA should be carefully considered.

Clinical and Patient-reported Outcomes in Patients with Psoriatic Arthritis (PsA) by Body Surface Area Affected by Psoriasis: Results from the Corrona PsA/Spondyloarthritis Registry.

OBJECTIVE: Psoriatic arthritis (PsA) is commonly comorbid with psoriasis; the extent of skin lesions is a major contributor to psoriatic disease severity/burden. We evaluated whether extent of skin involvement with psoriasis [body surface area (BSA) > 3% vs ≤ 3%] affects overall clinical and patient-reported outcomes (PRO) in patients with PsA. METHODS: Using the Corrona PsA/Spondyloarthritis Registry, patient characteristics, disease activity, and PRO at registry enrollment were assessed for patients with PsA aged ≥ 18 years with BSA > 3% versus ≤ 3%. Regression models were used to evaluate associations of BSA level with outcome [modified minimal disease activity (MDA), Health Assessment Questionnaire (HAQ) score, patient-reported pain and fatigue, and the Work Productivity and Activity Impairment questionnaire score]. Adjustments were made for age, sex, race, body mass index, disease duration, and history of biologics, disease-modifying antirheumatic drug, and prednisone use. RESULTS: This analysis included 1240 patients with PsA with known BSA level (n = 451, BSA > 3%; n = 789, BSA ≤ 3%). After adjusting for potential confounding variables, patients with BSA > 3% versus ≤ 3% had greater patient-reported pain and fatigue and higher HAQ scores (p = 2.33 × 10-8, p = 0.002, and p = 1.21 × 10-7, respectively), were 1.7× more likely not to be in modified MDA (95% CI 1.21-2.41, p = 0.002), and were 2.1× more likely to have overall work impairment (1.37-3.21, p = 0.0001). CONCLUSION: These Corrona Registry data show that substantial skin involvement (BSA > 3%) is associated with greater PsA disease burden, underscoring the importance of assessing and effectively managing psoriasis in patients with PsA because this may be a contributing factor in PsA severity.

Development of a flattening filter free multiple source model for use as an independent, Monte Carlo, dose calculation, quality assurance tool for clinical trials.

PURPOSE: The Imaging and Radiation Oncology Core-Houston (IROC-H) Quality Assurance Center (formerly the Radiological Physics Center) has reported varying levels of compliance from their anthropomorphic phantom auditing program. IROC-H studies have suggested that one source of disagreement between institution submitted calculated doses and measurement is the accuracy of the institution's treatment planning system dose calculations and heterogeneity corrections used. In order to audit this step of the radiation therapy treatment process, an independent dose calculation tool is needed. METHODS: Monte Carlo multiple source models for Varian flattening filter free (FFF) 6 MV and FFF 10 MV therapeutic x-ray beams were commissioned based on central axis depth dose data from a 10 × 10 cm2 field size and dose profiles for a 40 × 40 cm2 field size. The models were validated against open-field measurements in a water tank for field sizes ranging from 3 × 3 cm2 to 40 × 40 cm2 . The models were then benchmarked against IROC-H's anthropomorphic head and neck phantom and lung phantom measurements. RESULTS: Validation results, assessed with a ±2%/2 mm gamma criterion, showed average agreement of 99.9% and 99.0% for central axis depth dose data for FFF 6 MV and FFF 10 MV models, respectively. Dose profile agreement using the same evaluation technique averaged 97.8% and 97.9% for the respective models. Phantom benchmarking comparisons were evaluated with a ±3%/2 mm gamma criterion, and agreement averaged 90.1% and 90.8% for the respective models. CONCLUSIONS: Multiple source models for Varian FFF 6 MV and FFF 10 MV beams have been developed, validated, and benchmarked for inclusion in an independent dose calculation quality assurance tool for use in clinical trial audits.